In vitro antibiofilm activity of the freshwater bryozoan Hyalinella punctata: a case study of Pseudomonas aeruginosa PAO1

The antibiofilm and possible antiquorum sensing effects against the strain Pseudomonas aeruginosa PAO1 of five crude extracts of the freshwater bryozoan Hyalinella punctata (Hancock, 1850) were evaluated in vitro for the first time. H. punctata ethyl acetate extract (HpEtAc) exhibited the highest antibiofilm activity reducing the biofilm formation of P. aeruginosa PAO1 in the range of 80.63–88.13%. While all tested extracts reduced the twitching motility of the aforementioned bacterial strain, HpEtAc showed to be the most effective. Finally, at a concentration of 0.5 MIC, the same extract mostly inhibited the production of pyocyanin by P. aeruginosa PAO1 (71.53%). In comparison both with the positive controls used (streptomycin and ampicillin, 67.13 and 69.77%, respectively), HpEtAc was found to inhibit pyocyanin in a higher extent. An extensive chemical characterisation of this particular extract may result in isolation and identification of novel lead compounds targeting P. aeruginosa, an opportunistic human pathogen.     

Synthesis,Characterization and Biological Investigations of Half-Sandwich Ruthenium(II) Complexes Containing Benzimidazole Moiety

Half-sandwich Ru(II) complexes belong to group of biologically active metallo-compounds with promising antimicrobial and anticancer activity. Herein, we report the synthesis and characterization of arene ruthenium complexes containing benzimidazole moiety, namely, [(η⁶-p-cymene)RuCl(bimCOO)] (1) and [(η⁶-p-cymene)RuCl₂(bim)] (2) (where bimCOO = benzimidazole-2-carboxylate and bim = 1-H-benzimidazole). The compounds were characterized by ¹H NMR, ¹³C NMR, IR, UV–vis and CV. Molecular structures of the complexes were determined by SC-XRD analysis, and the results indicated the presence of a pseudo-tetrahedral (piano stool) geometry. Interactions in the crystals of the Ru complexes using the Hirshfeld surface analysis were also examined. In addition, the biological studies of the complexes, such as antimicrobial assays (against planktonic and adherent microbes), cytotoxicity and lipophilicity, were performed. Antibacterial activity of the complexes was evaluated against S. aureus, E. coli, P. aeruginosa PAO1 and LES B58. Cytotoxic activity was tested against primary human fibroblasts and adenocarcinoma human alveolar basal epithelial cells. Obtained biological results show that the ruthenium compounds have bacteriostatic activity toward Pseudomonas aeruginosa PAO1 strain and are not toxic to normal cells. A molecular docking study was applied as a predictive source of information about the plausibility of examined structures binding with HSA as a transporting system.     

Synthesis and Antibacterial Activity of New Azole,Diazole and Triazole Derivatives Based on p-Aminobenzoic Acid

The p-aminobenzoic acid was applied for the synthesis of substituted 1-phenyl-5-oxopyrrolidine derivatives containing benzimidazole, azole, oxadiazole, triazole, dihydrazone, and dithiosemicarbazide moieties in the structure. All the obtained compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Salmonella enteritidis, Escherichia coli, and Pseudomonas aeruginosa by using MIC and MBC assays. This study showed a good bactericidal activity of γ-amino acid and benzimidazoles derivatives. The antimicrobial activity of the most promising compounds was higher than ampicillin. Furthermore, two benzimidazoles demonstrated good antimicrobial activity against L. monocytogenes (MIC 15.62 µg/mL) that was four times more potent than ampicillin (MIC 65 µg/mL). Further studies are needed to better understand the mechanism of the antimicrobial activity as well as to generate antimicrobial compounds based on the 1-phenyl-5-oxopyrrolidine scaffold.     

Discovery of Novel Sultone Fused Berberine Derivatives as Promising Tdp1 Inhibitors

A new type of berberine derivatives was obtained by the reaction of berberrubine with aliphatic sulfonyl chlorides. The new polycyclic compounds have a sultone ring condensed to C and D rings of a protoberberine core. The reaction conditions were developed to facilitate the formation of sultones with high yields without by-product formation. Thus, it was shown that the order of addition of reagents affects the composition of the reaction products: when sulfochlorides are added to berberrubine, their corresponding 9-O-sulfonates are predominantly formed; when berberrubine is added to pre-generated sulfenes, sultones are the only products. The reaction was shown to proceed stereo-selectively and the cycle configuration was confirmed by 2D NMR spectroscopy. The inhibitory activity of the synthesized sultones and their 12-brominated analogs against the DNA-repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1), an important target for a potential antitumor therapy, was studied. All derivatives were active in the micromolar and submicromolar range, in contrast to the acyclic analogs and 9-O-sulfonates, which were inactive. The significance of the sultone cycle and bromine substituent in binding with the enzyme was confirmed using molecular modeling. The active inhibitors are mostly non-toxic to the HeLa cancer cell line, and several ligands show synergy with topotecan, a topoisomerase 1 poison in clinical use. Thus, novel berberine derivatives can be considered as candidates for adjuvant therapy against cancer.     

Enhancement of Antibiotic Activity by 1,8-Naphthyridine Derivatives against Multi-Resistant Bacterial Strains

The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure–activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.     

Microwave-Assisted Synthesis,Biological Activity Evaluation,Molecular Docking,and ADMET Studies of Some Novel Pyrrolo [2,3-b] Pyrrole Derivatives

Novel pyrrolo [2,3-b] pyrrole derivatives were synthesized and their hypolipidemic activity was assessed in hyperlipidemic rats. The chemical structures of the new derivatives were confirmed through spectral analysis. Compounds 5 and 6 were revealed to be the most effective hypolipidemic agents, with considerable hypocholesterolemic and hypotriglyceridemic effects. They appear to be promising candidates for creating new powerful derivatives with anti-atherosclerotic and hypolipidemic properties. As for antimicrobial activity, some of the tested compounds showed moderate activity against Pseudomonas aeruginosa: compound 2 revealed an MIC value of 50 μg/mL, compared to 25 μg/mL for ciprofloxacin. Compound 3 showed good antimicrobial activity against Staphylococcus aureus, comparable to ciprofloxacin, and roughly half the activity of ampicillin, according to MIC values. Compound 2 has an MIC approximately 25% of that of clotrimazole against Candida albicans. Compound 2 also showed the highest antioxidant activity with 59% inhibition of radical scavenging activity. Additionally, the cytotoxic activity of these new derivatives 1–7 was investigated and most of them showed good anticancer activity against the three tested cell lines.     

Designing Functionally Substituted Pyridine-Carbohydrazides for Potent Antibacterial and Devouring Antifungal Effect on Multidrug Resistant (MDR) Strains

The emergence of multidrug-resistant (MDR) pathogens and the gradual depletion of available antibiotics have exacerbated the need for novel antimicrobial agents with minimal toxicity. Herein, we report functionally substituted pyridine carbohydrazide with remarkable antimicrobial effect on multi-drug resistant strains. In the series, compound 6 had potent activity against four MDR strains of Candida spp., with minimum inhibitory concentration (MIC) values being in the range of 16–24 µg/mL and percentage inhibition up to 92.57%, which was exceptional when compared to broad-spectrum antifungal drug fluconazole (MIC = 20 µg/mL, 81.88% inhibition). Substitution of the octyl chain in 6 with a shorter butyl chain resulted in a significant anti-bacterial effect of 4 against Pseudomonas aeruginosa (ATCC 27853), the MIC value being 2-fold superior to the standard combination of ampicillin/cloxacillin. Time-kill kinetics assays were used to discern the efficacy and pharmacodynamics of the potent compounds. Further, hemolysis tests confirmed that both compounds had better safety profiles than the standard drugs. Besides, molecular docking simulations were used to further explore their mode of interaction with target proteins. Overall results suggest that these compounds have the potential to become promising antimicrobial drugs against MDR strains.     

Novel 3-Acetyl-2,5-disubstituted-1,3,4-oxadiazolines: Synthesis and Biological Activity

The aim of our study was the two-stage synthesis of 1,3,4-oxadiazole derivatives. The first step was the synthesis of hydrazide–hydrazones from 3-methyl-4-nitrobenzhydrazide and the corresponding substituted aromatic aldehydes. Then, the synthesized hydrazide–hydrazones were cyclized with acetic anhydride to obtain new 3-acetyl-2,3-disubstituted-1,3,4-oxadiazolines. All of obtained compounds were tested in in vitro assays to establish their potential antimicrobial activity and cytotoxicity. Our results indicated that few of the newly synthesized compounds had some antimicrobial activity, mainly compounds 20 and 37 towards all used reference bacterial strains (except Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa) and fungi. These substances showed a strong or powerful bactericidal effect, especially against Staphylococcus spp. belonging to Gram-positive bacteria. Compound 37 was active against Staphylococcus epidermidis at minimal inhibitory concentration (MIC) = 0.48 µg/mL and was characterized by low cytotoxicity. This compound possessed quinolin-4-yl substituent in the second position of 1,3,4-oxadiazole ring and 3-methyl-4-nitrophenyl in position 5. High effectiveness and safety of these derivatives make them promising candidates as antimicrobial agents. Whereas the compound 20 with the 5-iodofurane substituent in position 2 of the 1,3,4-oxadiazole ring showed the greatest activity against S. epidermidis at MIC = 1.95 µg/mL.     

Substrate specificity and function of acetylpolyamine amidohydrolases from <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis>

Background

Pseudomonas aeruginosa, a Gram-negative, aerobic coccobacillus bacterium is an opportunistic human pathogen and worldwide the fourth most common cause of hospital-acquired infections which are often high mortality such as ventilator-associated pneumoniae. The polyamine metabolism of P. aeruginosa and particularly the deacetylation of acetylpolyamines has been little studied up to now. Results with other bacterial pathogens e.g., Y. pestis suggest that polyamines may be involved in the formation of biofilms or confer resistance against certain antibiotics.

Results

To elucidate the role of acetylpolyamines and their enzymatic deacetylation in more detail, all three putative acetylpolyamine amidohydrolases (APAHs) from P. aeruginosa have been expressed in enzymatic active form. The APAHs PA0321 and PA1409 are shown to be true polyamine deacetylases, whereas PA3774 is not able to deacetylate acetylated polyamines. Every APAH can hydrolyze trifluoroacetylated lysine-derivatives, but only PA1409 and much more efficiently PA3774 can also process the plain acetylated lysine substrate. P. aeruginosa is able to utilize acetylcadaverine and acetylputrescine as a carbon source under glucose starvation. If either the PA0321 or the PA1409 but not the PA3774 gene is disrupted, the growth of P. aeruginosa is reduced and delayed. In addition, we were able to show that the APAH inhibitors SAHA and SATFMK induce biofilm formation in both PA14 and PAO1 wildtype strains.

Conclusions

P. aeruginosa has two functional APAHs, PA0321 and PA1409 which enable the utilization of acetylpolyamines for the metabolism of P. aeruginosa. In contrast, the physiological role of the predicted APAH, PA3774, remains to be elucidated. Its ability to deacetylate synthetic acetylated lysine substrates points to a protein deacetylation functionality with yet unknown substrates.

     

Computational discovery of putative quorum sensing inhibitors against LasR and RhlR receptor proteins of Pseudomonas aeruginosa

Drugs have been discovered in the past mainly either by identification of active components from traditional remedies or by unpredicted discovery. A key motivation for the study of structure based virtual screening is the exploitation of such information to design targeted drugs. In this study, structure based virtual screening was used in search for putative quorum sensing inhibitors (QSI) of Pseudomonas aeruginosa. The virtual screening programme Glide version 5.5 was applied to screen 1,920 natural compounds/drugs against LasR and RhlR receptor proteins of P. aeruginosa. Based on the results of in silico docking analysis, five top ranking compounds namely rosmarinic acid, naringin, chlorogenic acid, morin and mangiferin were subjected to in vitro bioassays against laboratory strain PAO1 and two more antibiotic resistant clinical isolates, P. aeruginosa AS1 (GU447237) and P. aeruginosa AS2 (GU447238). Among the five compounds studied, except mangiferin other four compounds showed significant inhibition in the production of protease, elastase and hemolysin. Further, all the five compounds potentially inhibited the biofilm related behaviours. This interaction study provided promising ligands to inhibit the quorum sensing (QS) mediated virulence factors production in P. aeruginosa.     

Quorum sensing regulates electric current generation of Pseudomonas aeruginosa PA14 in bioelectrochemical systems

Here, we show that quorum sensing (QS) modulates the current generation of the anode-respiring bacterium Pseudomonas aeruginosa because it controls the production of phenazines, which mediate the electron transfer to the anode. The current generation by a wildtype (WT) strain P. aeruginosa PA14 and the GacS/GacA protein-regulatory mutant retS was investigated under different environmental conditions. The retS mutant generated significantly higher current (45-fold) than the WT under anaerobic conditions. Anaerobic current generation by the WT was 28-fold higher with extraneously supplied lactones (a QS-signaling molecule). Compared to anaerobic conditions, the WT with some oxygen (microaerobic conditions) exhibited enhanced phenazine production (39-fold) and current levels (48-fold). Iron-rich medium and microaerobic conditions had a negative impact on current generation by retS. All these results were directly linked to QS activity in P. aeruginosa, thus, demonstrating the importance of this bacterial communication system for current generation in BESs. We also show that BESs represent a new tool for real-time investigation of phenazine-related QS activity.     

Role of the Quorum Sensing Mechanism in the Response of Pseudomonas aeruginosa to Lethal and Sublethal UVA Irradiation

The role of quorum sensing (QS) in the response of Pseudomonas aeruginosa to UVA radiation was investigated in the PAO1 strain and derivatives defective in the synthesis of the QS signals 3OC12-HSL (lasI strain), C4-HSL (rhlI strain) or both (lasI rhlI strain). Cell viability measurements demonstrated that the double mutant was significantly more sensitive to UVA than single mutants, which in turn showed reduced cell survival with regard to the PAO1 strain. Irradiation under nitrogen atmosphere and chemiluminescence measurements indicated the oxidative nature of the UVA-induced damage. The activity of the antioxidant enzymes catalase and superoxide dismutase was assayed in these strains before and after irradiation, and a strong correlation between catalase levels and UVA sensitivity was observed. When a sublethal UVA dose was applied to PAO1, a growth delay was observed and this mechanism depended on the rhl system. Moreover, low doses of UVA irradiation triplicated the level of C4-HSL in log PAO1 cells. It is concluded that QS is fundamental in the defense against the toxic effects of UVA in P. aeruginosa. The induction of the QS system by UVA independently of cell density could function as an adaptative strategy to withstand this hostile environmental condition.     

Inhibitory Effect of Multivalent Rhamnobiosides on Recombinant Horseshoe Crab Plasma Lectin Interactions with Pseudomonas aeruginosa PAO1

To evaluate the molecular interaction of recombinant horseshoe crab plasma lectin (rHPL) with Pseudomonas aeruginosa PAO1, multivalent rhamnobioside derivatives were designed. Eight rhamnoclusters with three or four α(1–3)‐rhamnobiosides attached to different central cores, such as methyl gallate, pentaerythritol, and N‐Boc Tris, through either an ethylene glycol or a tetraethylene glycol linker, were assembled in two consecutive azide–alkyne cycloaddition click reactions. The synthetic method embraced the preparation of two α(1–3)‐rhamnobiosides with different linker arms and their conjugation, in stoichiometric or substoichiometric amounts, to propargyl ether‐functionalized tri‐ or tetravalent scaffolds. A divalent derivative and two self‐assembling rhamnobiosides were also prepared. The different architectures and valences of the rhamnoclusters provided an opportunity to evaluate the impact of topology and valency on the binding properties toward rHPL. Inhibitory ELISA data showed that all covalently linked rhamnoclusters could inhibit P. aeruginosa PAO1 recognition activity of rHPL with high efficacy. Trivalent rhamnobiosides showed a stronger inhibitory effect on P. aeruginosa PAO1 binding, and the more flexible clusters on a pentaerythritol or a Tris core were superior to the less flexible methyl gallate‐based clusters. Interestingly, the length of the linker arms had a very low impact on the binding ability of the rhamnoclusters. Herein, the two trivalent derivatives on an N‐Boc protected Tris central core were the best inhibitors. The self‐assembling amphiphilic rhamnobioside derivatives were found to display no multivalent effect.     

Evaluation of ent-kaurenoic acid derivatives for their anticariogenic activity

Ent-kaur-16(17)-en-19-oic acid (kaurenoic acid, KA) is a tetracyclic diterpene prototype for natural anticaries agents. Six KA derivatives were prepared and their antimicrobial activity against the main microorganisms involved in the caries process evaluated. The sodium salt of KA (KA-Na) was the most active, displaying very promising MIC values for most pathogens. Time-kill assays against the primary causative agent of caries (Streptococcus mutans) indicated that KA and KA-Na only inhibited growth in the first 12 h, suggesting a bacteriostatic effect. After this period (12-24 h), their bactericidal effect was clearly noted. KA and KA-Na showed no synergy when combined with the gold standard anticariogenic (chlorhexidine dihydrochloride, CHD) in the checkerboard assays against S. mutans.     

Heterologous Co-expression of accA, fabD, and Thioesterase Genes for Improving Long-Chain Fatty Acid Production in Pseudomonas aeruginosa and Escherichia coli

The goal of the present study was to increase the content of intracellular long-chain fatty acids in two bacterial strains, Pseudomonas aeruginosa PA14 and Escherichia coli K-12 MG1655, by co-overexpressing essential enzymes that are involved in the fatty acid synthesis metabolic pathway. Recently, microbial fatty acids and their derivatives have been receiving increasing attention as an alternative source of fuel. By introducing two genes (accA and fabD) of P. aeruginosa into the two bacterial strains and by co-expressing with them the fatty acyl?Cacyl carrier protein thioesterase gene of Streptococcus pyogenes (strain MGAS10270), we have engineered recombinant strains that are efficient producers of long-chain fatty acids (C16 and C18). The recombinant strains exhibit a 1.3?C1.7-fold increase in the production of long-chain fatty acids over the wild-type strains. To enhance the production of total long-chain fatty acids, we researched the carbon sources for optimized culture conditions and results were used for post-culture incubation period. E. coli SGJS17 (containing the accA, fabD, and thioesterase genes) produced the highest content of intracellular total fatty acids; in particular, the unsaturated fatty acid content was about 20-fold higher than that in the wild-type E. coli.     

In Vitro Influence of ZnO,CrZnO, RuZnO,and BaZnO Nanomaterials on Bacterial Growth

In this work, ZnO, CrZnO, RuZnO, and BaZnO nanomaterials were synthesized and characterized in order to study their antibacterial activity. The agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays were used to determine the antibacterial activity of the fabricated nanomaterials against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC35218, Klebsiella pneumoniae ATCC 7000603, and Pseudomonas aeruginosa ATCC 278533. The well-diffusion test revealed significant antibacterial activity against all investigated bacteria when compared to vancomycin at a concentration of 1 mg/mL. The most susceptible bacteria to BaZnO, RuZnO, and CrZnO were Staphylococcus aureus (15.5 ± 0.5 mm), Pseudomonas aeruginosa (19.2 ± 0.5 mm), and Pseudomonas aeruginosa (19.7 ± 0.5), respectively. The MIC values indicated that they were in the range of 0.02 to 0.2 mg/mL. The MBC values showed that the tested bacteria’s growth could be inhibited at concentrations ranging from 0.2 to 2.0 mg/mL. According to the MBC/MIC ratio, BaZnO, RuZnO, and CrZnO exhibit bacteriostatic effects and may target bacterial protein synthesis based on the results of the tolerance test. This study shows the efficacy of the above-mentioned nanoparticles on bacterial growth. Further biotechnological and toxicological studies on the nanoparticles fabricated here are recommended to benefit from these findings.     

An insight into antimicrobial activity of the freshwater bryozoan Pectinatella magnifica

The antimicrobial activity of five crude extracts of the freshwater bryozoan Pectinatella magnifica (Leidy, 1851) was evaluated in vitro for the first time. P. magnifica acetone extract exhibited the highest antibacterial activity (minimum inhibitory concentrations (MIC) 0.004–0.350 mg/mL and MBC 0.007–0.500 mg/mL), while its methanol extract showed the most promising antifungal activity (MIC 0.03–0.12 mg/mL and MFC 0.06–0.25 mg/mL). Furthermore, at a concentration of 0.25 MIC, the methanol extract reduced biofilm formation of the bacterial strain Pseudomonas aeruginosa PAO1 in a considerable extent (59.14%). FTIR spectra of the most active extracts indicate the presence of carbonyl compounds, long-chain alcohols and/or sterols. According to the experimental data obtained, P. magnifica methanol extract may be considered as a good resource of novel natural products with potent antibiofilm activity against the bacterium well known for its resistance.     

In vitro anti-quorum sensing activity of phytol

Anti-quorum sensing activity of the diterpene phytol was evaluated in vitro for the first time. This compound (at three sub-MIC concentrations – 0.5, 0.25 and 0.125 MIC, respectively) reduced the formation of Pseudomonas aeruginosa PAO1 biofilm in the range of 74.00–84.33% exhibiting higher activity than the both positive controls used, streptomycin and ampicillin. Phytol (0.5 MIC) also effectively reduced P. aeruginosa twitching and flagella motility. Indeed, the bacteria treated were incapable of producing a twitching zone and had almost round, smooth and regular colony edges. Finally, the tested compound (0.5 MIC) exhibited good P. aeruginosa pyocyanin inhibitory activity (51.94%) practically to the same extent as streptomycin (52.09%). According to the experimental data obtained, this phytol property may inspire design of medical foods targeting P. aeruginosa quorum sensing activity.     

Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation

Background: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. Methods: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF₃-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. Results: All compounds showed antibacterial activity with MIC in range of 0.12–0.75 mg/mL and MBC at 0.25–>1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. Conclusion: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF₃ substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds.     

Multivalent calixarene-based C-fucosyl derivative: a new Pseudomonas aeruginosa biofilm inhibitor

The first example of multivalent conjugate in which four α-l-C-fucosyl units are clustered by means of a calix[4]arene platform was designed as a new potential Pseudomonas aeruginosa biofilm inhibitor. The anti-biofilm activity of the synthesized compound (6) against PAO1 strain was assayed and it was found to be dose-dependent. The presence of the fucose cluster improves the biofilm inhibitor efficiency as proven by the lower inhibitor activity of the analogous glycyl-calix[4]arene derivative (3) lacking in the fucose moieties.